Gastric carcinoma (GC) is one of the most common and deadest cancers with ˜1 million diagnoses and ˜0.7 million deaths each year worldwide1, with high incidence in Eastern Asia2. However, very few effective treatment options are available beyond surgery for the majority of GC patients. Trastuzumab (Herceptin®), a monoclonal antibody targeting HER2, is the only approved target therapy, but is limited to a small fraction of GC patients with higher HER2 (EGFR2) gene expression3 and amplification. The recently approved drugs that can demonstrate significant benefits in GC could be particularly attractive to meet such an urgent need. EGFR, also referred to as ERBB1/HER1, belongs to the same family of HER2 and is a receptor tyrosine kinase (RTK) expressed in epithelia cancers, including colorectal carcinoma (CRC), GC and non-small cell lung carcinoma (NSCLC), etc. Cetuximab is a monoclonal antibody, that binds to EGFR and blocks its ligand induced downstream signaling, thus inhibiting cell proliferation. Cetuximab was approved by Food and Drug Administration (FDA) for treating EGFR-expressing metastatic CRC (mCRC) without activating KRAS mutations at codons 12/134, and squamous cell carcinoma of head and neck (SCCHN)5, but Cetuximab has yet to be approved for treatment for GC. There are several phase II clinical trials on the combination treatments of cetuximab/chemotherapy agents for advanced GC but the studies have yet to demonstrate significant superior clinical benefit over the current standard of care (SOC)6-8. A randomized controlled phase III trial sponsored by Merck Serona has been recently reported to fail to meet its primary endpoint (NCT00678535: Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer, or EXPAND).
New effective target therapy is therefore urgently needed. The present invention provides this and other advantages.